Mutational analysis to map residues responsible for differences in neutralization sensitivity and resistance in Envs from subject 113035.

<p>Amino acids from the neutralization-sensitive clone (007) were systematically inserted into the neutralization-resistant Env (045). (A) Effect of amino acid polymorphisms on neutralization by plasma from four HIV-1 infected subjects. The neutralizing antibody titer (IC₅₀) is defined as the reciprocal of the plasma dilution that produces a 50% inhibition in target cell infection. Values in bold represent significant neutralization titers that are at least three times greater than those observed against the negative control (aMLV). Panel A, open rectangle, indicates neutralization titers for the wildtype resistant (wtR) clone; black rectangle, indicates neutralization titers for the wildtype sensitive (wtS) clone; gray rectangle, indicates the single amino acid substitution that converted the neutralization-resistant Env into a neutralization-sensitive Env. NI, indicates a non-infectious mutant. Panels B and C represent graphs and statistical analysis of neutralization of 113035 mutants with the T500208 and Z23 plasma, respectively. Panels B and C, closed square (■) indicates neutralization titers of wtS clone 007; open square (□) indicates neutralization titer of wtR clone 045. Open triangles (△) indicate neutralization titers of wtR clone 045 incorporating the N150S mutation. Closed circles (●) indicate neutralization by the other mutants listed in panel A. Statistical significance was calculated using an unpaired t test.